Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMRDZ4X)

• Drug Name: Dabigatran etexilate Drug Info
• Synonyms: BIBR-1048; 211915-06-9; Dabigatran etexilate mesilate; ethyl N-[(2-{[(4-{N'-[(hexyloxy)carbonyl]carbamimidoyl}phenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl]-N-pyridin-2-yl-beta-alaninate; Dabigatran etexilate methanesulfonate; BIBR-1048 (Dabigatran); UNII-2E18WX195X; BIBR1048; BIBR-1048-BS-RS1; CHEBI:70746; 2E18WX195X; cc-72; DSSTox_CID_31470; DSSTox_RID_97355; DSSTox_GSID_57681; SCHEMBL505829; DTXSID4057681; Dabigatran etexilate (USAN/INN); MolPort-016-633-287; EBD35035; Tox21_113924; BDBM504

Indication

Disease Entry	ICD 11	Status	REF
Venous thromboembolism	BD72	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 135565674
  CAS Number: CAS 211915-06-9
  TTD Drug ID: DMRDZ4X
  INTEDE Drug ID: DR0400
  ACDINA Drug ID: D00162

Molecule-Related Drug Atlas

Drug(s) Metabolized By UDP-glucuronosyltransferase 2B7 (UGT2B7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[4]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[5]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[6]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[7]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[8]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[6]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[9]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[10]
Ezetimibe	DM7A8TW	Atherosclerosis	BD40	Approved	[11]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[12]

Drug(s) Metabolized By UDP-glucuronosyltransferase 1A9 (UGT1A9)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[13]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[6]
Mycophenolate mofetil	DMPQAGE	Hepatosplenic T-cell lymphoma		Approved	[16]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[6]
Ibuprofen	DM8VCBE	Dysmenorrhea	GA34.3	Approved	[6]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[17]
Nateglinide	DMLK2QH	Diabetic complication	5A2Y	Approved	[6]
Haloperidol	DM96SE0	Delirium		Approved	[6]

Drug(s) Metabolized By Carboxylesterase 1 (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[18]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[19]
Candesartan	DMRK8OT	Chronic heart failure	BD1Z	Approved	[20]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[21]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[22]
PSI-7977	DMLSUWZ	HCV 1-6 infection	1E51	Approved	[23]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[24]
Dexmethylphenidate	DMUQE2A	Attention deficit hyperactivity disorder	6A05.Z	Approved	[25]
MK-4827	DMLYGH4	Ovarian cancer	2C73	Phase 3	[26]
Pradaxa	DM2ZYX9	Stroke	8B20	Phase 3	[27]

Drug(s) Metabolized By Carboxylesterase 2 (CES2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[28]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[29]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[24]
Pradaxa	DM2ZYX9	Stroke	8B20	Phase 3	[27]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Substrate	[2]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[2]
Carboxylesterase 1 (CES1) Main DME	DEB30C5	EST1_HUMAN	Substrate	[3]
Carboxylesterase 2 (CES2) Main DME	DETHCPD	EST2_HUMAN	Substrate	[3]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75.
• [3] Pharmacogenomics of novel direct oral anticoagulants: newly identified genes and genetic variants. J Pers Med. 2019 Jan 17;9(1). pii: E7.
• [4] Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncol. 2014 Jan;10(1):107-22.
• [5] Determination of UDP-glucuronosyltransferase UGT2B7 activity in human liver microsomes by ultra-performance liquid chromatography with MS detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 1;870(1):84-90.
• [6] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [7] Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
• [8] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [9] Pitavastatin: a review in hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168.
• [10] Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9.
• [11] Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-94.
• [12] Pharmacogenomics of statins: understanding susceptibility to adverse effects. Pharmgenomics Pers Med. 2016 Oct 3;9:97-106.
• [13] Polymorphic expression of UGT1A9 is associated with variable acetaminophen glucuronidation in neonates: a population pharmacokinetic and pharmacogenetic study. Clin Pharmacokinet. 2018 Oct;57(10):1325-1336.
• [14] Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos. 2005 Jul;33(7):1027-35.
• [15] Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4.
• [16] The evolution of population pharmacokinetic models to describe the enterohepatic recycling of mycophenolic acid in solid organ transplantation and autoimmune disease. Clin Pharmacokinet. 2011 Jan;50(1):1-24.
• [17] The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83.
• [18] Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23.
• [19] Absorption and cleavage of enalapril, a carboxyl ester prodrug, in the rat intestine: in vitro, in situ intestinal perfusion and portal vein cannulation models. Biopharm Drug Dispos. 2015 Sep;36(6):385-397.
• [20] Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
• [21] Effect of carboxylesterase 1 c.428G>A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8.
• [22] Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76.
• [23] Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
• [24] Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
• [25] Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat. 2006 Dec;2(4):467-73.
• [26] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [27] Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704.
• [28] Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug Metab Dispos. 2004 May;32(5):505-11.
• [29] In vitro metabolism of dexamethasone cipecilate, a novel synthetic corticosteroid, in human liver and nasal mucosa. Xenobiotica. 2011 Oct;41(10):874-84.